Research in this Section consists of studies on the physical and chemical properties of proteins of biological interest and the roles of ligand binding and protein-protein interactions in enzyme catalysis and regulation. (1) Interactions of divalent cations, substrates, and inhibitors with glutamine synthetase from Escherichia coli have been studied by calorimetry, ultracentrifugation, equilibrium dialysis, pH, spectral, thermal perturbation, and kinetic techniques. L-Methionine-SR-sulfoximine (a transition state analog) promotes both local and gross conformational differences between unadenylylated and adenylylated enzymes; thermodynamic parameters for the binding of the S and R diastereoisomers of this analog differ. The unadenylylated Mn-enzyme catalyzes a novel, AMP-dependent (reversible) synthesis of pyrophosphate and L-glutamate from orthophosphate and L-glutamine. (2) A calorimetric estimate of the enthalpy change for the substrate-promoted conformational transition of aspartate transcarbamoylase from E. coli is -6 kcal/mol. From heats of subunit assembly in the presence and absence of a bisubstrate analog, the substrate-linked subunit interaction enthalpy change is plus 22 kcal/mol.